Fish oil exacerbates colitis in SMAD3 mice.

There are seemingly disparate results from epidemiologic studies regarding associations between fish or marine n-3 polyunsaturated fatty acids (PUFA) intake and colorectal cancer risk. A recent report by Woodworth et al. (1) provides clarity for why a potential etiologic factor, such as fish intake, appears protective for colorectal cancer in some populations, but risk enhancing in other populations. For example, we (2) and others (3, 4) have reported positive associations in Chinese populations, whereas a meta-analysis of prospective studies conducted in Western populations reported a statistically nonsignificant inverse association (5; Table 1). Woodworth et al. demonstrated that a marine PUFA diet increased the risk of colon adenocarcinoma in mice with Helicobacter hepaticus–induced colitis (1). Woodworth et al. concluded that mice with active colitis that were fed high doses of the marine n-3 PUFA, docosahexaenoic acid had impaired immune function and thus were less equipped to mount a successful response to H. hepaticus infection (1). We put forth a novel hypothesis, inspired by these findings, that marine n-3 PUFAs are associated with increased risk of colorectal cancer in humans when in the presence of H. pyloriinduced hypergastrinemia. Hypergastrinemia is a direct result of increased serum gastrin levels caused by gastric H. pylori infection. The prevalence of H. pylori infection varies worldwide, with the highest prevalence in East and Southeast Asian regions and the lowest in Western-developed regions. Hypergastrinemia has proliferative effects on colonic mucosa, and animal data support a role for hypergastrinemia in the progression of colon adenomas (6). There is also prospective epidemiologic data supporting an association between elevated gastrin levels and colorectal cancer risk (7).